NM_001378609.3:c.3277A>C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BS1_Supporting
The NM_001378609.3(OTOGL):āc.3277A>Cā(p.Asn1093His) variant causes a missense change. The variant allele was found at a frequency of 0.0000215 in 1,584,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001378609.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOGL | NM_001378609.3 | c.3277A>C | p.Asn1093His | missense_variant | Exon 29 of 59 | ENST00000547103.7 | NP_001365538.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOGL | ENST00000547103.7 | c.3277A>C | p.Asn1093His | missense_variant | Exon 29 of 59 | 5 | NM_001378609.3 | ENSP00000447211.2 | ||
OTOGL | ENST00000646859.1 | c.3142A>C | p.Asn1048His | missense_variant | Exon 33 of 63 | ENSP00000496036.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000209 AC: 30AN: 1432236Hom.: 0 Cov.: 30 AF XY: 0.0000154 AC XY: 11AN XY: 712774
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152296Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
The OTOGL p.Asn1084His variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs867315415), ClinVar (classified as VUS by Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Asn1084 residue is conserved in mammals but not in other organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
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In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
not specified Uncertain:1
The p.Asn1084His variant in OTOGL has not been previously reported in individual s with hearing loss or in large population studies. Computational prediction too ls and conservation analysis do not provide strong support for or against an imp act to the protein. In summary, the clinical significance of the p.Asn1048His va riant is uncertain. -
Autosomal recessive nonsyndromic hearing loss 84B Uncertain:1
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at